本文選題：喉 + 氣管��； 參考：《第四軍醫(yī)大學(xué)》2011年博士論文

【摘要】：各種原因?qū)е碌暮怼夤苋睋p是耳鼻咽喉科的常見病與多發(fā)病,對于喉氣管缺損的修復(fù)與重建目前仍無標(biāo)準(zhǔn)的治療。由于喉氣管缺損的原因與嚴(yán)重程度不同給臨床治療帶來了極大的困難。多年來研究喉氣管缺損的修復(fù)與重建以關(guān)注假體材料的選擇、加工與重建方式為主,近年來一些學(xué)者亦通過動物模型研究各種修復(fù)材料與長段氣管缺損的重建方法,發(fā)現(xiàn)假體的血管化與上皮化仍是我們目前臨床面臨的挑戰(zhàn)。然而,新型介穩(wěn)定β-鈦合金材料對于喉、氣管缺損的修復(fù)與重建目前尚無報(bào)道。 目的:觀察并探討新型介穩(wěn)定β-鈦合金(TLM)材料在犬的喉、氣管缺損修復(fù)與重建中的有效性,為喉、氣管缺損的治療提供一種可選擇的生物材料,同時為臨床治療提供新的理論依據(jù)。 方法:1.采用激光切割方法,將鈦合金板制成微多孔結(jié)構(gòu)。高壓消毒后,置于6孔板中,將小鼠NIH-3T3單細(xì)胞懸液按1×105細(xì)胞/毫升的密度加入材料表面培養(yǎng),四小時后取一片材料做掃描電鏡觀察。測量孔徑大小并做圖像分析,計(jì)算孔隙率。并對材料表面的細(xì)胞活力與形態(tài)進(jìn)行觀察。 2.取5只犬,將犬的喉與氣管充分暴露,切除環(huán)狀軟骨及第1氣管軟骨環(huán)的前1/3形成喉前裂開,將“◇”形的生物材料替代切除的部分喉氣管組織,按計(jì)劃術(shù)后3至6個月對受試動物進(jìn)行氣管鏡檢測。3.采用多孔TLM合金作為10只雜種犬的前喉氣管組織再生支架。修復(fù)體長度為20mm,修復(fù)與重建前環(huán)狀軟骨及第1氣管環(huán)的缺損,進(jìn)一步評估TLM合金在該治療中的有效性。4.取20只雜種犬,隨機(jī)分成2組:TLM合金組與Ti-2組,每組各10只。切除環(huán)狀軟骨及第1、2氣管軟骨環(huán),將兩種“C”形的管狀生物材料替代切除的部分喉氣管缺損,按計(jì)劃術(shù)后1、4及12周對受試動物分期進(jìn)行喉氣管鏡檢查、CT掃描及組織病理學(xué)檢測。5.選擇5只雜種犬行頸部切除5厘米長段氣管,將多孔TLM制作成人氣管形狀以修復(fù)環(huán)周氣管缺損。按計(jì)劃植入3至8個月后處死動物行內(nèi)鏡檢查、CT掃描和病理分析。 結(jié)果:1. TLM合金表面凹凸不平,呈多孔結(jié)構(gòu),孔徑為70～90μm,孔隙率為32%。細(xì)胞表現(xiàn)出有足突和偽足的正常細(xì)胞形狀。2.術(shù)后在所有受試犬中均未見到任何的氣道阻塞。未見修復(fù)體的移位暴露,內(nèi)表面無肉芽組織生長及吻合口裂開。3.一只犬于術(shù)后一周復(fù)查因麻醉意外而死亡;一只犬于術(shù)后約一個月因肺部感染而死亡;剩下的8只犬均于術(shù)后3至8個月處死;處死時發(fā)現(xiàn)所有修復(fù)體與周圍宿主組織融合。術(shù)后內(nèi)鏡檢查顯示:無1只發(fā)生氣道狹窄,其中4只長有肉芽組織,一只發(fā)現(xiàn)多孔TLM合金板暴露,未觀察到吻合口的裂開。然而,所有這些犬均無臨床癥狀。光鏡與電鏡結(jié)果顯示:在假體內(nèi)腔表面有一個正常的粘膜組織生長,及在重建的喉氣管內(nèi)腔位置未觀察到任何的可見肉芽組織。4.術(shù)后在兩組中均未出現(xiàn)吻合口漏。兩種材料的修復(fù)體均表現(xiàn)出了良好的生物機(jī)械強(qiáng)度。組織學(xué)檢測結(jié)果顯示:TLM合金修復(fù)體周圍的成纖維細(xì)胞在早期就從網(wǎng)孔長入,且修復(fù)體內(nèi)腔吻合口部位可見有豐富的纖毛柱狀上皮,纖毛分布密度也均勻,而在Ti-2組中,修復(fù)體周圍組織長入較慢,且上皮分布明顯不均。5.該假體的機(jī)械性能好,假體與周圍組織結(jié)合緊密,結(jié)果充分展示了假體的生物相容性與耐腐蝕性,且沒有產(chǎn)生任何的氣管狹窄與空氣的滲漏,并允許少量的肉芽組織正常長入氣管內(nèi)腔。 結(jié)論:1.首次采用TLM合金材料應(yīng)用于喉、氣管缺損的修復(fù)與重建。TLM合金材料具有良好的生物相容性、耐腐蝕性及機(jī)械性能,特別是其彈性模量(30～50Gpa)最接近骨與軟骨,為喉氣管缺損的重建提供了良好的應(yīng)力分布。2.首次采用激光切割方法,將鈦合金板制成微多直孔結(jié)構(gòu)的喉氣管假體,其微孔大小定位在70-90um,孔隙率為30%～35%,厚度為0.5mm。假體植入后發(fā)現(xiàn)在早期階段因周圍結(jié)締組織從網(wǎng)孔的長入而保證了氣密性,且其微血管的形成為假體腔內(nèi)的快速上皮化提供了條件,從而最終克服了假體內(nèi)腔的狹窄。同時發(fā)現(xiàn)本重建過程比目前所有試驗(yàn)的其它多孔材料要快。我們進(jìn)一步證明上皮化結(jié)果與氣管兩端及假體孔隙進(jìn)入的含豐富毛細(xì)血管網(wǎng)的結(jié)締組織有關(guān)。3.TLM合金是一種很有潛力的新型喉氣管缺損的修復(fù)材料,對未來臨床的應(yīng)用具有進(jìn)一步深入研究的意義與價(jià)值。
[Abstract]:The larynx and trachea defect is a common and frequently occurring disease in the Department of Otolaryngology for various reasons. There is still no standard treatment for the repair and reconstruction of the laryngotracheal defect. The reasons for the laryngotracheal defect and the severity of the laryngotracheal defect have brought great difficulties to the clinical treatment. The selection of body materials, processing and reconstruction are the main methods. In recent years, some scholars have also studied the reconstruction methods of various repair materials and long segment trachea defects through animal models. It is found that the vascularization and epithelialization of the prosthesis are still the challenges we face. However, the new metastable beta titanium alloy has been used to repair the larynx and the trachea defect. There is no report on the reconstruction.
Objective: To observe and investigate the effectiveness of a new mediate stable beta titanium alloy (TLM) in the repair and reconstruction of laryngeal and tracheal defects in dogs, and to provide a choice of biomaterials for the treatment of laryngeal and tracheal defects, and provide a new theoretical basis for clinical treatment.
Methods: 1. the titanium alloy plate was made into micro porous structure by laser cutting. After high pressure disinfection, it was placed in the 6 hole plate. The mouse NIH-3T3 single cell suspension was cultured on the surface of the material with the density of 1 x 105 cell per milliliter. After four hours, a piece of material was taken for scanning electron microscope. The pore size was measured and the porosity was calculated. The porosity was calculated and the porosity was calculated. The cell viability and morphology were observed on the surface of the material.
2. in 5 dogs, the dogs were fully exposed to the larynx and trachea, the cricoid cartilage and the anterior 1/3 of the 1 tracheal cartilaginous ring were removed to form the anterior larynx. The tracheal tissue of the resected part of the laryngoscope was replaced by the biomaterial of the shape of the larynx. The tracheal microscopic examination of the subjects was performed for 3 to 6 months after the planned operation and the porous TLM alloy was used as the anterior larynx of the 10 hybrid dogs. Endotracheal tissue regeneration. Repair body length was 20mm, repair and reconstruction of cricoid cartilage and 1 tracheal ring defects, further evaluate the effectiveness of TLM alloy in the treatment of.4. to take 20 hybrid dogs, randomly divided into 2 groups: TLM alloy group and Ti-2 group, 10 in each group. Excision of cricoid cartilage and 1,2 tracheal cartilage ring, two "C" shaped tubes The resected partial laryngotracheal defects were replaced by biomaterials, and laryngotrachoscopy was performed at 1,4 and 12 weeks after the planned operation. CT scanning and histopathological detection of.5. selected 5 hybrid dogs with 5 cm long trachea excised in the neck. The porous TLM was made to repair the tracheal defect of the circumferential trachea. 3 to 8 were implanted as planned. After a month, the animals were sacrificed for endoscopy, CT scan and pathological analysis.
Results: the surface of 1. TLM alloy was uneven and porous structure, the pore size was 70~90 mu m, and the porosity was 32%. cells showing the normal cell shape of the foot process and the puppet foot. No airway obstruction was seen in all the dogs after the operation. No transfer exposure of the repair body, the inner surface without granulation tissue growth and the anastomotic opening of.3. a dog were not seen. A dog died a week after an anaesthesia; one dog died about one month after the operation due to lung infection; the remaining 8 dogs were killed 3 to 8 months after the operation; all the prostheses were found to be fused with the surrounding host tissues at the time of death. The postoperative endoscopy showed that there were no 1 strictures, 4 of them had granulation tissue, and one found The perforated TLM alloy plate was exposed and no anastomotic cleavage was observed. However, all of these dogs had no clinical symptoms. The results of light and electron microscopy showed that there was a normal tissue growth on the surface of the prosthesis, and no visible anastomosis in the two groups was not observed in any of the visible granulation tissue.4. in the rebuilt laryngotracheal cavity. The prosthesis of the two materials showed good mechanical strength. The histological examination showed that the fibroblasts around the TLM alloy prosthesis grew from the mesh in the early stage, and the plentiful ciliated columnar epithelium was seen in the anastomotic site of the repair body, and the density of the cilia was evenly distributed in the Ti-2 group. The mechanical performance of the prosthesis is good and the prosthesis is closely associated with the surrounding tissue. The result fully demonstrates the biocompatibility and corrosion resistance of the prosthesis, and does not produce any tracheal stenosis and air leakage, and allows a small amount of granulation tissue to grow normally into the endotracheal cavity.
Conclusion: 1. TLM alloy materials were used for the first time in the larynx. The repair and reconstruction of the defect of the trachea has good biocompatibility, corrosion resistance and mechanical properties, especially its modulus of elasticity (30 ~ 50Gpa) is closest to the bone and cartilage, which provides a good stress distribution for the reconstruction of laryngeal and tracheal defects,.2. is the first time to use laser cutting side. The titanium alloy plate is made into a laryngotracheal prosthesis with microporous structure of the titanium alloy plate. The micropore size is located at 70-90um, the porosity is 30% to 35%, and the thickness is 0.5mm. implant. It is found that the air tightness is ensured by the growth of the surrounding connective tissue from the mesh in the early stage, and the formation of the microvessel provides a strip for rapid epithelial cells in the false body cavity. It finally overcomes the stenosis of the inner cavity of the prosthesis. It is also found that the reconstruction process is faster than all the other porous materials currently tested. We further demonstrate that the results of the epithelialization are a potential new type of laryngotracheal deficiency associated with.3.TLM gold in the connective tissue with the rich capillary network at both ends of the trachea and the pores. The damaged repair materials will have further significance and value for future clinical application.
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R762

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